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1.
Int J Pharm ; 660: 124289, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38825171

RESUMO

The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone. This is an option that offers critical advantages to the ongoing opioid crisis, including ease of distribution and easy administration, with little to no need for intervention by clinicians. Nonetheless, this approach by itself needs augmentation to meet pharmacokinetic delivery attributes desired for a viable clinical alternative to existing market dosage forms. In this study, we report the success of an optimized iontophoresis-coupled naloxone loaded dissolving microneedle patch which had facilitated a 12- fold increase in average cumulative permeation and a 6-fold increase in drug flux over a conventional dissolving microneedle patch within 60 min of application (p < 0.05). This translates to a 30 % decrease in dose requirement in a mechanistically predicted microneedle patch established to be able to achieve the desired early plasma concentration time profile needed in an opioid overdose emergency. Applying a predictive mathematical model, we describe an iontophoresis-coupled microneedle patch design capable of meeting the desired pharmacokinetic profile for a viable naloxone delivery form through skin.


Assuntos
Administração Cutânea , Iontoforese , Naloxona , Antagonistas de Entorpecentes , Agulhas , Absorção Cutânea , Adesivo Transdérmico , Naloxona/administração & dosagem , Naloxona/farmacocinética , Iontoforese/métodos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/farmacocinética , Animais , Sistemas de Liberação de Medicamentos , Polímeros/química , Microinjeções/métodos , Masculino , Pele/metabolismo , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética
2.
Artigo em Russo | MEDLINE | ID: mdl-38934954

RESUMO

Functional gastrointestinal disorders, which had an impact on the dentofacial system (pain, loose teeth and falling out of them) in patients who have had COVID-19, drew the close attention of specialists of different profiles. The pathogenesis of worsening post-COVID edentulism is insufficiently studied, as many issues of adequate therapy remain unsolved, in which the role of non-drug technologies in the treatment of dental patients who have suffered from COVID-19 is extremely high. OBJECTIVE: To describe the mechanism of action and clinical effectiveness of the developed combined physiotherapy method, including the induced technique of piracetam iontophoresis on the frontooccipital technic and acupuncture laser therapy in dental patients with complaints of edentulism progression after COVID-19 on the basis of the analysis of single studies on the post-COVID loss of teeth treatment. MATERIAL AND METHODS: A number of patients equal 120 who complained of tooth loss after COVID-19 during the past 6 months were examined. The following initial and end points were considered: dental bleeding and inflammation scores, vascular and endothelial dysfunction markers - levels of intercellular adhesion molecules and their receptors (SlCAM-1, SVCAM-1, VEGF-A, ET-1) before and after treatment. RESULTS: Negative correlation between VEGF-A (pg/ml) concentration in peripheral blood serum and sVCAM-1 (ng/ml) level in the examined patients (r=0.4830, p<0.05) and strong inverse correlation between slCAM-1 (ng/ml) level and sVCAM-1 (r=0.7696, p<0.01) have been established. More significant effects after application of the combined induced method on the head's structures and laser acupuncture have been noted than after acupuncture laser exposure and after inducing technique separately, namely in the form of dental inflammation score correction by 1.76 times (p<0.001), decrease of bleeding score by 2.6 (p<0.05), decrease of concentration of SVCAM-1 by 1.7 times and SlCAM-1 by 2 times (p<0.001), increase of endothelin level by 1.7 times as well as the initial low VEGF-A (pg/ml) by 1.5 times (p<0.01). CONCLUSION: The developed physiotherapeutic complex, which includes laser acupuncture physiotherapy and induced technique of 5% piracetam iontophoresis, can potentially be considered as a physioprophylactic and therapeutic model of post-COVID edentulism.


Assuntos
COVID-19 , Modalidades de Fisioterapia , Humanos , COVID-19/terapia , COVID-19/complicações , COVID-19/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Iontoforese/métodos , SARS-CoV-2 , Adulto , Terapia por Acupuntura/métodos , Terapia Combinada , Idoso
3.
Pharm Res ; 41(6): 1183-1199, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38849712

RESUMO

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.


Assuntos
Administração Cutânea , Anti-Inflamatórios , Dexametasona , Sistemas de Liberação de Medicamentos , Edema , Iontoforese , Agulhas , Absorção Cutânea , Pele , Animais , Iontoforese/métodos , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Dexametasona/análogos & derivados , Ratos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Edema/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Pele/metabolismo , Pele/efeitos dos fármacos , Masculino , Liberação Controlada de Fármacos , Inflamação/tratamento farmacológico , Ratos Sprague-Dawley
4.
Int J Pharm ; 654: 123992, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38479485

RESUMO

Linagliptin is a dipeptidyl peptidase-4 inhibitor used for the management of type-2 diabetes. US FDA-approved products are available exclusively as oral tablets. The inherent drawbacks of the oral administration route necessitate exploring delivery strategies via other routes. In this study, we investigated the feasibility of transdermal administration of linagliptin through various approaches. We compared chemical penetration enhancers (oleic acid, oleyl alcohol, and isopropyl myristate) and physical enhancement techniques (iontophoresis, sonophoresis, microneedles, laser, and microdermabrasion) to understand their potential to improve transdermal delivery of linagliptin. To our knowledge, this is the first reported comparison of chemical and physical enhancement techniques for the transdermal delivery of a moderately lipophilic molecule. All physical enhancement techniques caused a significant reduction in the transepithelial electrical resistance of the skin samples. Disruption of the skin's structure post-treatment with physical enhancement techniques was further confirmed using characterization techniques such as dye binding, histology, and confocal microscopy. In vitro permeation testing (IVPT) demonstrated that the passive delivery of linagliptin across the skin was < 5 µg/sq.cm. Two penetration enhancers - oleic acid (93.39 ± 8.34 µg/sq.cm.) and oleyl alcohol (424.73 ± 42.86 µg/sq.cm.), and three physical techniques - iontophoresis (53.05 ± 0.79 µg/sq.cm.), sonophoresis (141.13 ± 34.22 µg/sq.cm.), and laser (555.11 ± 78.97 µg/sq.cm.) exceeded the desired target delivery for therapeutic effect. This study established that linagliptin is an excellent candidate for transdermal delivery and thoroughly compared chemical penetration and physical transdermal delivery strategies.


Assuntos
Álcoois Graxos , Linagliptina , Absorção Cutânea , Administração Cutânea , Linagliptina/metabolismo , Ácido Oleico/metabolismo , Pele/metabolismo , Iontoforese/métodos , Sistemas de Liberação de Medicamentos/métodos
5.
Clin Exp Dermatol ; 49(6): 599-606, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38323717

RESUMO

BACKGROUND: Palmoplantar psoriasis (PPP) is a localized variant of psoriasis that may be resistant to topical therapy, owing to the poor penetrability of topical agents at this anatomical site. Modalities that enhance localized cutaneous delivery of drugs could help to solve this problem. Iontophoresis is one such procedure that augments transdermal drug delivery, thus enabling better and expeditious therapeutic outcomes. OBJECTIVE: To compare the therapeutic efficacy and safety of iontophoresis with tretinoin 0.05% cream and tacrolimus 0.1% ointment in treating patients with PPP. METHODS: Sixty patients with PPP (28 males and 32 females, age range 8-76 years) were enrolled and randomly assigned to one of two groups comprising 30 patients each. One group (12 males and 18 females) received iontophoresis with tretinoin 0.05% cream; the other (16 males and 14 females) received iontophoresis treatment with tacrolimus 0.1% ointment. Both groups received treatment weekly from baseline until 4 weeks and then fortnightly at weeks 6 and 8. Clinical images were taken at each visit and improvement of psoriasis was evaluated using the erythema, scaling, induration and fissuring (ESIF) score. The percentage reduction in ESIF score was also assessed on completion of treatment and the grade of improvement noted for each patient. RESULTS: Twenty-seven patients in the iontophoresis with tretinoin 0.05% cream group and 29 in the iontophoresis treatment with tacrolimus 0.1% ointment group completed the study. The mean (SD) ESIF score in the former decreased significantly from 8.7 (2) at baseline to 3.2 (1.7) at the study endpoint (P < 0.001). Similarly, in the latter group, there was a substantial reduction in mean (SD) ESIF score from 8.2 (1.9) at baseline to 3.3 (1.1) at the study end (P < 0.001). No significant adverse effects were encountered in either treatment arm. CONCLUSIONS: Iontophoresis using tretinoin and tacrolimus was found to be effective and safe for the treatment of PPP. Although iontophoresis with tretinoin showed slightly better results than with tacrolimus, these were not statistically significant.


Assuntos
Administração Cutânea , Iontoforese , Pomadas , Psoríase , Tacrolimo , Tretinoína , Humanos , Feminino , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Iontoforese/métodos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Criança , Psoríase/tratamento farmacológico , Tretinoína/administração & dosagem , Tretinoína/uso terapêutico , Adulto Jovem , Resultado do Tratamento , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Terapia Combinada
6.
Int Ophthalmol ; 44(1): 89, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366000

RESUMO

PURPOSE: To investigate the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis and to analyse the possible mechanism. METHODS: Forty rabbits were divided into five groups randomly: 0.1% riboflavin-balanced salt solution (BSS) by iontophoresis group, 0.1% riboflavin-saline solution by iontophoresis group, 0.1% riboflavin-zinc gluconate solution by iontophoresis group, 0.1% riboflavin-calcium gluconate solution by iontophoresis group and classical riboflavin instillation after corneal de-epithelialization as the control group. The riboflavin concentrations in corneal stroma were determined and compared by high-performance liquid chromatography (HPLC) after removing epithelium and endothelium. RESULTS: Iontophoretic delivery of a 0.1% riboflavin-calcium gluconate solution was the closest to the effect of classical de-epithelialization. The other solvents were unsufficient at enhancing the permeability of the riboflavin. CONCLUSION: Calcium ions can promote the penetrability of riboflavin into the corneal stroma by iontophoresis.


Assuntos
Substância Própria , Epitélio Corneano , Animais , Coelhos , Iontoforese/métodos , Cálcio , Gluconato de Cálcio , Fármacos Fotossensibilizantes/uso terapêutico , Reagentes de Ligações Cruzadas , Riboflavina , Córnea , Íons
8.
Mol Pharm ; 21(1): 234-244, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38060844

RESUMO

Assessing drug disposition in the skin after the application of a topical formulation is difficult. It is hypothesized that reverse iontophoresis (RI), which can extract charged/polar molecules for monitoring purposes, may provide a noninvasive approach for the assessment of local drug bioavailability. The passive and RI extraction of salicylic acid (SA) and nicotine (NIC) from porcine skin in vitro was assessed after a simple solution of the former and a transdermal patch of the latter had been applied for 24 and 8 h, respectively. Immediately after this "passive skin loading", the amount of drug in the stratum corneum (SC) and "viable" tissue (VT) was measured either (a) after tape-stripping and subsequent solvent extraction of both skin layers or (b) following RI extraction over 4 h. Parallel experiments were then performed in vivo in healthy volunteers; in this case, the VT was not sampled and the skin loading period for NIC was only 4 h. RI extraction of both drugs was significantly higher (in vitro and in vivo) than that achieved passively, and the cumulative RI extraction profiles as a function of time were mathematically analyzed using a straightforward compartmental model. Best-fit estimates of drug amounts in the SC and VT (ASC,0 and AVT,0, respectively) at the end of "loading" and two first-order rate constants describing transfer between the model compartments were then determined. The in vitro predictions of ASC,0 and AVT,0 were in excellent agreement with the experimental results, as was the value of the former in vivo. The rate constants derived from the in vitro and in vivo results were also similar. In summary, the results provide proof-of-concept that the RI method has the potential to noninvasively assess relevant metrics of drug bioavailability in the skin.


Assuntos
Iontoforese , Pele , Suínos , Animais , Humanos , Iontoforese/métodos , Disponibilidade Biológica , Pele/metabolismo , Absorção Cutânea , Epiderme
9.
J Pediatr Ophthalmol Strabismus ; 61(1): 44-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37227009

RESUMO

PURPOSE: To evaluate the clinical characteristics of pediatric patients with progression of keratoconus after accelerated iontophoresis-assisted epithelium-on corneal cross-linking (I-ON CXL) and to assess the efficacy and safety of re-treatment using accelerated epithelium-off CXL (epi-OFF CXL). METHODS: Sixteen eyes of 16 patients (mean age: 14.6 ± 2.5 years) with keratoconus underwent I-ON CXL. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, maximum keratometry index (Kmax), minimum corneal thickness, elevation front and elevation back measured at the thinnest point, total higher order aberrations root main square (HOA RMS), coma RMS, and spherical aberration. An increment of Kmax greater than 1.00 diopter (D) and a decrease of greater than 20 µm in pachymetry were considered to determine the progression of keratoconus. Patients with progression of keratoconus after I-ON CXL were re-treated using an epi-OFF CXL protocol. RESULTS: Two years after I-ON CXL, 12 patients showed progression of keratoconus, whereas 4 patients were stable. There was significant worsening of Kmax (P = .04) and steepest keratometric reading (P = .01). Furthermore, a significant correlation was documented between progression of keratoconus and age (P = .02). These patients were re-treated using an epi-OFF protocol and after 2 years all patients were stable, and a statistically significant reduction of the mean Kmax (P = .007), HOA RMS (P = .05), and coma RMS (P = 05) was observed. CONCLUSIONS: I-ON CXL was ineffective in the treatment of pediatric keratoconus in younger children, whereas it had an efficacy of 2 years in older children. Re-treatment using epi-OFF CXL proved effective to halt progression of keratoconus after I-ON CXL failure. [J Pediatr Ophthalmol Strabismus. 2024;61(1):44-50.].


Assuntos
Ceratocone , Fotoquimioterapia , Humanos , Criança , Adolescente , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Crosslinking Corneano , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Iontoforese/métodos , Raios Ultravioleta , Coma/tratamento farmacológico , Riboflavina/uso terapêutico , Topografia da Córnea/métodos , Paquimetria Corneana , Reagentes de Ligações Cruzadas/uso terapêutico , Colágeno
10.
Int J Pharm ; 648: 123617, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977289

RESUMO

Conventional treatments for cutaneous leishmaniasis, a neglected vector-borne infectious disease, can frequently lead to serious adverse effects. Paromomycin (PAR), an aminoglycoside antibiotic, has been suggested for the topical treatment of disease-related lesions, but even when formulated in high drug-loading dosage forms, presents controversial efficacy. The presence of five ionizable amino groups hinder its passive cutaneous penetration but make PAR an excellent candidate for iontophoretic delivery. The objective of this study was to verify the feasibility of using iontophoresis for cutaneous PAR delivery and to propose a topical passive drug delivery system that could be applied between iontophoretic treatments. For this, in vitro iontophoretic experiments evaluated different application durations (10, 30, and 360 min), current densities (0.1, 0.25, and 0.5 mA/cm2), PAR concentrations (0.5 and 1.0 %), and skin models (intact and impaired porcine skin). In addition, 1 % PAR hydrogel had its penetration profile compared to 15 % PAR ointment in passive transport. Results showed iontophoresis could deliver suitable PAR amounts to dermal layers, even in short times and with impaired skin. Biodistribution assays showed both iontophoretic transport and the proposed hydrogel delivered higher PAR amounts to deeper skin layers than conventional ointment, even though applying 15 times less drug. To our knowledge, this is the first report of PAR drug delivery enhancement by iontophoresis. In summary, the association of iontophoresis with a topical application of PAR gel seems appropriate for improving cutaneous leishmaniasis treatment.


Assuntos
Leishmaniose Cutânea , Paromomicina , Animais , Suínos , Paromomicina/metabolismo , Paromomicina/farmacologia , Iontoforese/métodos , Distribuição Tecidual , Pomadas/metabolismo , Pele/metabolismo , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Leishmaniose Cutânea/tratamento farmacológico , Hidrogéis/farmacologia
11.
J Control Release ; 364: 383-392, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37914000

RESUMO

Cancer is a leading cause of the death worldwide. However, the conventional cancer therapy still suffers from several limitations, such as systemic side effects, poor efficacy, and patient compliance due to limited accessibility to the tumor site. To address these issues, the localized drug delivery system has emerged as a promising approach. In this study, we developed an iontophoresis-based transdermal drug delivery system (TDDS) controlled by a smartphone application for cancer treatment. Iontophoresis, a low-intensity electric current-based TDDS, enhances drug permeation across the skin to provide potential for localized drug delivery and minimize systemic side effects. The fundamental mechanism of our system was modeled using finite element analysis and its performance was corroborated through the flow-through skin permeation tests using a plastic-based microfluidic chip. The results of in vitro cell experiments and skin deposition tests successfully demonstrated that our smartphone-controlled iontophoresis system significantly enhanced the drug permeation for cancer treatment. Therefore, this hand-held smartphone-based iontophoresis TDDS could be a powerful tool for self-administrated anticancer drug delivery applications.


Assuntos
Neoplasias , Absorção Cutânea , Humanos , Iontoforese/métodos , Smartphone , Administração Cutânea , Pele/metabolismo , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
12.
Int Ophthalmol ; 43(10): 3601-3607, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37395906

RESUMO

PURPOSE: To assess long-term efficacy and safety of iontophoresis-assisted transepithelial corneal cross-linking (I-CXL) for keratoconus. PATIENTS AND METHODS: Twenty-seven eyes of 21 patients (15 M, 6F) affected by progressive keratoconus were evaluated. All subjects were treated with iontophoresis-assisted transepithelial CXL. The patients were examined at baseline and each 6 months after the CXL procedure. Only subjects who completed the follow-up of 5 years were considered in this study. The main outcome measures were uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), corneal transparency and corneal parameters such as K-max, central corneal thickness (CCT) and at the thinnest point, and high-order ocular aberrations (HOAs). The ABCD system was used to determine the progression and re-progression of ectasia. SETTING: Ophthalmology Clinic, University Hospital of Messina, Messina, Italy. RESULTS: At 5 years, significant improvements of UCVA from 0.53 ± 0.33 logMAR to 0.4 ± 0.33 logMAR (p = 0.001) and HOAs (p = 0.01) were registered. No significant changes of CDVA (p = 0.4), K-max (p = 0.75), CCT (p = 0.5) were observed at the end of follow-up period. The ABCD system showed re-progression in 25.9% of eyes after 5 years. No adverse events such as corneal opacities and infections were reported. CONCLUSIONS: Iontophoresis-assisted transepithelial CXL resulted to be safe and effective to stabilize progressive keratoconus in adults at a long-term follow-up.


Assuntos
Ceratocone , Fotoquimioterapia , Adulto , Humanos , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Crosslinking Corneano , Iontoforese/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Topografia da Córnea , Reagentes de Ligações Cruzadas/uso terapêutico , Riboflavina/uso terapêutico , Raios Ultravioleta
13.
Artigo em Inglês | MEDLINE | ID: mdl-37436009

RESUMO

Background Primary palmar hyperhidrosis causes a lot of problems for patients and negatively affects their quality of life. Currently, iontophoresis with tap water and aluminum chloride hexahydrate is used for primary palmar hyperhidrosis. Yet, little evidence exists about iontophoresis with aluminum chloride hexahydrate in the form of gel. This study investigated the effect of aluminum chloride hexahydrate gel iontophoresis compared to tap water iontophoresis on primary palmar hyperhidrosis. Methods In this randomised controlled trial study, 32 patients with primary palmar hyperhidrosis were divided randomly into two groups (n = 16). Participants received 7 sessions of iontophoresis with aluminum chloride hexahydrate gel or tap water every other day on the dominant hand. The sweating rate was measured by gravimetry and iodine-starch tests before and after the last treatment session. Results Following the iontophoresis, the rate of sweating in both hands in the two groups was significantly reduced (P < 0.001). However, the sweating rate in the treated hand and the non-treated hand showed no significant difference. There was no significant difference observed in sweating rate reduction between both groups over time, but the larger effect size values observed in the aluminum chloride hexahydrate gel iontophoresis group may suggest the superiority of this gel over tap water in reducing the rate of sweating. Limitations Further investigations with longer follow-up are needed to confirm the hypothesis regarding the effectiveness of aluminum chloride hexahydrate gel iontophoresis over other types of iontophoresis. In addition, contraindications of iontophoresis such as pregnancy, pacemakers, and epilepsy should be considered. Conclusion The present study provides preliminary evidence suggesting that aluminum chloride hexahydrate gel iontophoresis is an effective alternative treatment to decrease sweating rate in extended areas with fewer side effects in patients with primary palmar hyperhidrosis.


Assuntos
Hiperidrose , Gravidez , Feminino , Humanos , Cloreto de Alumínio/uso terapêutico , Hiperidrose/diagnóstico , Hiperidrose/tratamento farmacológico , Hiperidrose/etiologia , Iontoforese/métodos , Qualidade de Vida , Água , Alumínio/uso terapêutico
14.
Pharm Res ; 40(8): 2039-2049, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37186072

RESUMO

AIM: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. METHODS: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. RESULTS: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MNdi) compared to MN alone (MNdo). Histological examination of rat skin treated with vaccine laden MN (MNvo) and MN-iontophoresis combination (MNvi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MNvo and MNvi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MNvo and MNvi treatment, respectively. CONCLUSION: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously.


Assuntos
Vacina Antirrábica , Ratos , Animais , Cães , Iontoforese/métodos , Parafina , Sefarose , Administração Cutânea , Pele , Sistemas de Liberação de Medicamentos , Agulhas , Imunoglobulina G
15.
Pharm Res ; 40(8): 1977-1987, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37258949

RESUMO

PURPOSE: Iontophoresis is a noninvasive method that enhances drug delivery using an electric field. This method can improve drug delivery to the tissues in the oral cavity. The effects of iontophoresis on gingival drug delivery have not been investigated. The objectives of this study were to (a) determine the flux enhancement of model permeants across porcine and human gingiva during iontophoresis, (b) examine the transport mechanisms of gingival iontophoresis, and (c) evaluate the potential of iontophoretically enhanced delivery for three model drugs lidocaine, ketorolac, and chlorhexidine. METHODS: Passive and iontophoretic fluxes were determined with porcine and human gingiva using a modified Franz diffusion cell and model drugs and permeants. To investigate the transport mechanisms of iontophoresis, the enhancement from the direct-field effect was determined by positively and negatively charged model permeants. The electroosmosis enhancement effect was determined with neutral permeants of different molecular weight. The alteration of the gingival barrier due to electropermeabilization was evaluated using electrical resistance measurements. RESULTS: Significant flux enhancement was observed during gingival iontophoresis. The direct-field effect was the major mechanism governing the iontophoretic transport of the charged permeants. Electroosmosis was from anode to cathode. The effective pore radius of the iontophoretic transport pathways in the porcine gingiva was ~0.68 nm. Irreversible electropermeabilization was observed after 2 and 4 h of iontophoresis under the conditions studied. CONCLUSION: Iontophoresis could enhance drug delivery and reduce transport lag time, showing promise for gingival drug delivery.


Assuntos
Gengiva , Iontoforese , Humanos , Animais , Suínos , Iontoforese/métodos , Difusão , Eletro-Osmose , Sistemas de Liberação de Medicamentos , Administração Cutânea
16.
Biosens Bioelectron ; 235: 115406, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37210841

RESUMO

Reverse iontophoresis (RI) is a promising technology in the field of continuous glucose monitoring (CGM), offering significant advantages such as finger-stick-free operation, wearability, and non-invasiveness. In the glucose extraction process based on RI, the pH of the interstitial fluid (ISF) is a critical factor that needs further investigation, as it directly influences the accuracy of transdermal glucose monitoring. In this study, a theoretical analysis was conducted to investigate the mechanism by which pH affects the glucose extraction flux. Modeling and numerical simulations performed at different pH conditions indicated that the zeta potential was significantly impacted by the pH, thereby altering the direction and flux of the glucose iontophoretic extraction. A screen-printed glucose biosensor integrated with RI extraction electrodes was developed for ISF extraction and glucose monitoring. The accuracy and stability of the ISF extraction and glucose detection device were demonstrated with extraction experiments using different subdermal glucose concentrations ranging from 0 to 20 mM. The extraction results for different ISF pH values exhibited that at 5 mM and 10 mM subcutaneous glucose, the extracted glucose concentration was increased by 0.08212 mM and 0.14639 mM for every 1 pH unit increase, respectively. Furthermore, the normalized results for 5 mM and 10 mM glucose demonstrated a linear correlation, indicating considerable potential for incorporating a pH correction factor in the blood glucose prediction model used to calibrate glucose monitoring.


Assuntos
Técnicas Biossensoriais , Glucose , Glucose/análise , Glicemia/análise , Iontoforese/métodos , Automonitorização da Glicemia , Líquido Extracelular/química , Concentração de Íons de Hidrogênio
17.
Expert Opin Drug Deliv ; 20(6): 785-798, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37119173

RESUMO

INTRODUCTION: The skin is an attractive route for drug delivery. However, the stratum corneum is a critical limiting barrier for drug permeation. Nanoentrapment is a way to enhance cutaneous drug delivery, by diverse mechanisms, with a notable trend of nanoparticles accumulating into the hair follicles when topically applied. Iontophoresis is yet another way of increasing drug transport by applying a mild electrical field that preferentially passes through the hair follicles, for being the pathway of lower resistance. So, iontophoresis application to nanocarriers could further increase actives accumulation into the hair follicles, impacting cutaneous drug delivery. AREAS COVERED: In this review, the authors aimed to discuss the main factors impacting iontophoretic skin transport when combining nanocarriers with iontophoresis. We further provide an overview of the conditions in which this combination has been studied, the characteristics of nanosystems employed, and hypothesize why the association has succeeded or failed to enhance drug permeation. EXPERT OPINION: Nanocarriers and iontophoresis association can be promising to enhance cutaneous drug delivery. For better results, the electroosmotic contribution to the iontophoretic transport, mainly of negatively charged nanocarriers, charge density, formulation pH, and skin models should be considered. Moreover, the transfollicular pathway should be considered, especially when designing the nanocarriers.


Assuntos
Iontoforese , Pele , Preparações Farmacêuticas , Iontoforese/métodos , Pele/metabolismo , Administração Cutânea , Absorção Cutânea , Sistemas de Liberação de Medicamentos/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-36905622

RESUMO

BACKGROUND: The purpose of this study was to evaluate the effectiveness of tap water iontophoresis as a treatment for plantar hyperhidrosis. METHODS: Thirty participants living with idiopathic plantar hyperhidrosis and consented to undergo treatment using iontophoresis were recruited. The Hyperhidrosis Disease Severity Score was used to evaluate the severity of the condition before and after treatment. RESULTS: Tap water iontophoresis was found to be effective in the treatment of plantar hyperhidrosis in the study group (P = .005). CONCLUSIONS: Treatment with iontophoresis led to the reduction of disease severity and improvement of quality of life, and it is a safe, easy-to-use method with minimal side effects. This technique should be considered before the use of systemic or aggressive surgical interventions, which could have potentially more severe side effects.


Assuntos
Hiperidrose , Iontoforese , Humanos , Iontoforese/efeitos adversos , Iontoforese/métodos , Qualidade de Vida , Água
19.
Chem Commun (Camb) ; 59(23): 3339-3359, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36815500

RESUMO

The advancement and popularity of transdermal drug delivery (TDD) based on the physical transdermal enhancement technique (PTET) has opened a new paradigm for local tumor treatment. The drug can be directly delivered to the tumor site through the skin, thus avoiding the toxic side effects caused by the first-pass effect and achieving high patient compliance. Further development of PTETs has provided many options for antitumor drugs and laid the foundation for future applications of wearable closed-loop targeting drug delivery systems. In this highlight, the different types of PTETs and related mechanisms, and applications of PTET-related tumor detection and therapy are highlighted. According to their type and characteristics, PTETs are categorized as follows: (1) iontophoresis, (2) electroporation, (3) ultrasound, (4) thermal ablation, and (5) microneedles. PTET-related applications in the local treatment of tumors are categorized as follows: (1) melanoma, (2) breast tumor, (3) squamous cell carcinoma, (4) cervical tumor, and (5) others. The challenges and future prospects of existing PTETs are also discussed. This highlight will provide guidance for the design of PTET-based wearable closed-loop targeting drug delivery systems and personalized therapy for tumors.


Assuntos
Absorção Cutânea , Pele , Humanos , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Iontoforese/métodos , Preparações Farmacêuticas/metabolismo , Microinjeções/métodos
20.
Drug Deliv ; 30(1): 2165736, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36628545

RESUMO

Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.


Assuntos
Oftalmopatias , Iontoforese , Humanos , Preparações Farmacêuticas/metabolismo , Iontoforese/métodos , Olho , Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico
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